Author

Date of Award

Degree Type

Degree Name

School

Medical Sciences

Faculty

Faculty of Health, Engineering and Science

First Advisor

Professor Ralph Martins

Second Advisor

Dr Veer Gupta

Third Advisor

Associate Professor Giuseppe Verdile

Abstract

Alzheimer’s disease (AD) is increasing in prevalence due to increasing lifespan and altered lifestyle. It is the fourth major cause of death in Western countries, resulting in significant economic and social impact (Von Strauss, et al., 1999; Goate, 1997). There are no blood biomarkers currently accepted for the diagnosis of AD, and the identification of suitable biomarkers would eventually reduce the necessity for invasive, expensive and slow diagnostic procedures, as well as facilitate prognostic studies. An AD blood test would decrease the need for delaying diagnosis due to ambivalent presentation, and allow therapeutic intervention to commence at an earlier and more functional stage for the sufferer, thereby maximising the benefits of treatment. It is also feasible that a blood biomarker would be of use in the development of therapeutic treatments, which are currently inadequate.

Numerous studies have suggested that hyperinsulinemia and type II diabetes (DM2) significantly increase the risk of developing Alzheimer’s disease (AD). Therefore, much research interest has been aimed recently toward determining the putative common mechanisms of these conditions. One enzyme which has been implicated in both AD and DM2 is insulin degrading enzyme (IDE). This project focuses largely on the characterisation of plasma IDE expression and catalytic activity, to help determine potential role/s of IDE in the development of AD, and the suitability of IDE as an AD biomarker. Evidence is also provided to support the concept that IDE impairments may be the common factor that links AD, hyperinsulinemia and DM2.